瑞芬太尼后处理及其联合异丙酚后处理对大鼠肝脏缺血再灌注损伤的影响

Effects of remifentanil postconditioning and combined remifentanil-propofol postconditioning on liver isch- emia-reperfusion injury in rats

目的评价瑞芬太尼后处理及其联合异丙酚后处理对大鼠肝脏缺血再灌注损伤的影响。方法健康雄性SD大鼠30只，体重220～280g，采用随机数字表法，将其随机分为5组（n=6）：假手术组（Ⅰ组）、缺血再灌注组（Ⅱ组）、异丙酚后处理组（Ⅲ组）、瑞芬太尼后处理组（Ⅳ组）和异丙酚联合瑞芬太尼后处理组（Ⅴ组）。Ⅱ组～Ⅴ组采用夹闭门静脉和肝动脉30min的方法制备肝脏缺血再灌注损伤模型，Ⅰ组仅开腹。Ⅲ组、Ⅳ组和Ⅴ组再灌注即刻分别静脉输注异丙酚30mg·k^-1·h^-1、瑞芬太尼1μg·kg^-1·min^-1和异丙酚30mg·kg^-1h^-1＋瑞芬太尼1μg·kg^-1·min^-11h，Ⅱ组给予等容量生理盐水。于再灌注1h时采集静脉血样，测定血清AST、ALT活性、IL-8、IL-10的浓度，然后处死大鼠，取肝组织，测定肝细胞c-fos和c—jun表达，电镜下观察肝组织病理学结果。结果与Ⅰ组比较，Ⅱ组～Ⅴ组血清AST、ALT活性及IL-8、IL-10的浓度升高，肝细胞c-fos和c—jun表达上调（P〈0．05或0．01）；与Ⅱ组比较，Ⅲ组～Ⅴ组血清AST、ALT活性及IL-8浓度降低，IL-10浓度升高，肝细胞c-fos和c-fun表达下调（P〈0．05或0．01）；与Ⅲ组及Ⅳ组比较，Ⅴ组上述指标差异无统计学意义（P〉0．05）。Ⅲ组-Ⅴ组肝组织病理学损伤程度明显轻于Ⅱ组。结论瑞芬太尼后处理可减轻大鼠肝脏缺血再灌注损伤，联合异丙酚后处理时其效应与单独一种方法的效应相似，其机制与抑制炎性反应和肝细胞凋亡有关。

Objective To investigate the effects of remifentanil postconditioning and combined remifentanil-propofol postconditioning on liver ischcmia-reperfusion （I/R） injury in rats. Methods Thirty male SD rats weighing 220-280 g were randomly divided into 5 groups （n = 6 each） ： group sham operation （group Ⅰ ） ; group I/R （group Ⅱ ） ; group propofol postconditioning （group Ⅲ） ; group remifentanil postconditioning （group Ⅳ ） and group combined propofol-remifentanil postconditioning （group Ⅴ ）. In groups Ⅱ- Ⅴ the hepatic arteries and veins of middle and left were occluded for 30 min. In groups Ⅲ - Ⅴ propofol （ at 30 mg· kg^- 1·h^- 1 ） and/or remifentanil （ at 1 μg· kg^- 1 · min^- 1 ） were infused iv at the onset of reperfusion for 1 h. Blood samples were taken at the end of 1 h reperfusion for determination of serum AST, ALT activities and IL-8, IL-10 concentrations. The animals were sacrificed after blood sampling. Liver specimens were obtained for determination of c-fos and c-jun expression in liver ceils by immuno-histochemistry and microscopic examination with scanning electron microscope. Results Liver I/R significantly increased serum AST and ALT activities and IL-8 and IL-10 concentrations and c-los and c- jun expression in liver cells in group Ⅱ as compared with group Ⅰ . The serum AST and ALT activities, IL-8 concentration and the c-fos and c-jun expression in liver cells were significantly lower and the serum IL-10 concentra- tion was significantly higher in groups Ⅲ- Ⅴ than in group Ⅱ , but there were no significant differences among the groups Ⅲ- Ⅴ. The histo-pathological changes in the liver tissue were significantly attenuated in groups Ⅲ- Ⅴ as compared with group Ⅱ . Conclusion Postconditioning with remifentanil and/or propofol can attenuate liver I/R injury by inhibiting inflammatory response and apoptosis in the liver cells, but there is no significant difference in the protective effects induced by postconditioning with remifentanil or propofol alone or in combination.